Modulator of Apoptosis-1 is a Potential Therapeutic Target in Acute Ischemic Injury

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2018 Aug 23

PMID 30132384

Citations 4

Authors

Su Jing Chan

Hui Zhao

Kazuhide Hayakawa

Chou Chai

Chong Teik Tan

Jiawen Huang

Ran Tao

Gen Hamanaka

Thiruma V Arumugam

Eng H Lo

Victor Chun Kong Yu

PeterTsun-Hon Wong

Affiliations

Soon will be listed here.

Abstract

Modulator of apoptosis 1 (MOAP-1) is a Bax-associating protein highly enriched in the brain. In this study, we examined the role of MOAP-1 in promoting ischemic injuries following a stroke by investigating the consequences of MOAP-1 overexpression or deficiency in in vitro and in vivo models of ischemic stroke. MOAP-1 overexpressing SH-SY5Y cells showed significantly lower cell viability following oxygen and glucose deprivation (OGD) treatment when compared to control cells. Consistently, MOAP-1 primary cortical neurons were observed to be more resistant against OGD treatment than the MOAP-1 primary neurons. In the mouse transient middle cerebral artery occlusion (tMCAO) model, ischemia triggered MOAP-1/Bax association, suggested activation of the MOAP-1-dependent apoptotic cascade. MOAP-1 mice were found to exhibit reduced neuronal loss and smaller infarct volume 24 h after tMCAO when compared to MOAP-1 mice. Correspondingly, MOAP-1 mice also showed better integrity of neurological functions as demonstrated by their performance in the rotarod test. Therefore, both in vitro and in vivo data presented strongly support the conclusion that MOAP-1 is an important apoptotic modulator in ischemic injury. These results may suggest that a reduction of MOAP-1 function in the brain could be a potential therapeutic approach in the treatment of acute stroke.

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References

Balaganapathy P, Baik S, Mallilankaraman K, Sobey C, Jo D, Arumugam T . Interplay between Notch and p53 promotes neuronal cell death in ischemic stroke. J Cereb Blood Flow Metab. 2017; 38(10):1781-1795. PMC: 6168918. DOI: 10.1177/0271678X17715956. View

Tan C, Zhou Q, Su Y, Fu N, Chang H, Tao R . MOAP-1 Mediates Fas-Induced Apoptosis in Liver by Facilitating tBid Recruitment to Mitochondria. Cell Rep. 2016; 16(1):174-185. DOI: 10.1016/j.celrep.2016.05.068. View

Schuller M, Jenne D, Voltz R . The human PNMA family: novel neuronal proteins implicated in paraneoplastic neurological disease. J Neuroimmunol. 2005; 169(1-2):172-6. DOI: 10.1016/j.jneuroim.2005.08.019. View

Martin-Villalba A, Hahne M, Kleber S, Vogel J, Falk W, Schenkel J . Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Cell Death Differ. 2001; 8(7):679-86. DOI: 10.1038/sj.cdd.4400882. View

Chan S, Chai C, Lim T, Yamamoto M, Lo E, Lai M . Cystathionine β-synthase inhibition is a potential therapeutic approach to treatment of ischemic injury. ASN Neuro. 2015; 7(2). PMC: 4397212. DOI: 10.1177/1759091415578711. View

Tan K, Tan K, Chan S, Yee K, Bevort M, Ang K . MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J Biol Chem. 2000; 276(4):2802-7. DOI: 10.1074/jbc.M008955200. View

Gokce O, Stanley G, Treutlein B, Neff N, Camp J, Malenka R . Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Cell Rep. 2016; 16(4):1126-1137. PMC: 5004635. DOI: 10.1016/j.celrep.2016.06.059. View

Swanson R, Morton M, Savalos R, Davidson C, Sharp F . A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab. 1990; 10(2):290-3. DOI: 10.1038/jcbfm.1990.47. View

Hallenbeck J . The many faces of tumor necrosis factor in stroke. Nat Med. 2002; 8(12):1363-8. DOI: 10.1038/nm1202-1363. View

10.

Huang N, Zhang L, Tang W, Chen C, Yang C, Kornbluth S . The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1. J Cell Biol. 2012; 197(3):361-7. PMC: 3341153. DOI: 10.1083/jcb.201111141. View

11.

Yuan J . Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis. 2009; 14(4):469-77. PMC: 2745337. DOI: 10.1007/s10495-008-0304-8. View

12.

Pamenter M, Perkins G, McGinness A, Gu X, Ellisman M, Haddad G . Autophagy and apoptosis are differentially induced in neurons and astrocytes treated with an in vitro mimic of the ischemic penumbra. PLoS One. 2012; 7(12):e51469. PMC: 3520810. DOI: 10.1371/journal.pone.0051469. View

13.

Barteczek P, Li L, Ernst A, Bohler L, Marti H, Kunze R . Neuronal HIF-1α and HIF-2α deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke. J Cereb Blood Flow Metab. 2016; 37(1):291-306. PMC: 5363746. DOI: 10.1177/0271678X15624933. View

14.

Deng Y, He H, Yang L, Zhang P . Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke. Neural Regen Res. 2016; 11(7):1108-14. PMC: 4994453. DOI: 10.4103/1673-5374.187045. View

15.

Broughton B, Reutens D, Sobey C . Apoptotic mechanisms after cerebral ischemia. Stroke. 2009; 40(5):e331-9. DOI: 10.1161/STROKEAHA.108.531632. View

16.

Takaji M, Komatsu Y, Watakabe A, Hashikawa T, Yamamori T . Paraneoplastic antigen-like 5 gene (PNMA5) is preferentially expressed in the association areas in a primate specific manner. Cereb Cortex. 2009; 19(12):2865-79. PMC: 2774394. DOI: 10.1093/cercor/bhp062. View

17.

Youle R, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2007; 9(1):47-59. DOI: 10.1038/nrm2308. View

18.

Martin-Villalba A, Herr I, Jeremias I, Hahne M, Brandt R, Vogel J . CD95 ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J Neurosci. 1999; 19(10):3809-17. PMC: 6782733. View

19.

Shohami E, Ginis I, Hallenbeck J . Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev. 2000; 10(2):119-30. DOI: 10.1016/s1359-6101(99)00008-8. View

20.

Tasca C, Dal-Cim T, Cimarosti H . In vitro oxygen-glucose deprivation to study ischemic cell death. Methods Mol Biol. 2014; 1254:197-210. DOI: 10.1007/978-1-4939-2152-2_15. View